Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies
Abstract Trastuzumab deruxtecan (T-DXd) is approved for HER2-low (HER2 immunohistochemistry (IHC)1+ or 2+ with non-amplified in situ hybridization (ISH)), but not HER2-0 (IHC 0) metastatic breast cancer. The impact of repeat biopsies (Bxs) in identifying new potential candidates with triple negative...
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| Format: | Article |
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Nature Portfolio
2025-03-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00741-y |
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| author | Yael Bar Geoffrey Fell Aylin Dedeoglu Natalie Moffett Neelima Vidula Laura Spring Seth A. Wander Aditya Bardia Naomi Ko Beverly Moy Leif W. Ellisen Steven J. Isakoff |
| author_facet | Yael Bar Geoffrey Fell Aylin Dedeoglu Natalie Moffett Neelima Vidula Laura Spring Seth A. Wander Aditya Bardia Naomi Ko Beverly Moy Leif W. Ellisen Steven J. Isakoff |
| author_sort | Yael Bar |
| collection | DOAJ |
| description | Abstract Trastuzumab deruxtecan (T-DXd) is approved for HER2-low (HER2 immunohistochemistry (IHC)1+ or 2+ with non-amplified in situ hybridization (ISH)), but not HER2-0 (IHC 0) metastatic breast cancer. The impact of repeat biopsies (Bxs) in identifying new potential candidates with triple negative breast cancer (TNBC) for T-DXd treatment remains unknown. 512 consecutive patients with TNBC at diagnosis were included in the study cohort. Bxs were categorized as core, surgical, or metastatic based on the timing and method of biopsy (Bx) acquisition, and the total number of Bxs was determined for each patient. Additionally, matched biopsies were identified, and the rate of discordance in HER2 status was calculated. The proportion of patients with at least one HER2-low result increased as the number of successive Bxs increased [59%, 73%, 83%, 83%, and 100% when 1 (196 patients), 2 (231 patients), 3 (48 patients), 4 (29 patients), and ≥ 5 (8 patients) Bxs were obtained, respectively]. Among patients without a prior HER2-low result, approximately one-third demonstrated HER2-low status with each additional successive Bx. HER2 status exhibited variability between matched Bxs, with observed discordance rates of 26%, 44%, and 33% between matched core-surgical, early-metastatic, and two metastatic matched Bxs, respectively. Our findings indicate that HER2 status can vary between different Bxs taken during the disease course of patients with TNBC with the highest discordance rate observed between the primary and metastatic Bxs. For patients with metastastic HER2-0 TNBC, repeat Bxs can increase the chance of obtaining a HER2-low result, thereby offering patients a promising therapeutic option. |
| format | Article |
| id | doaj-art-b33b93aecba74dd4af4a862ae36be7e8 |
| institution | DOAJ |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-b33b93aecba74dd4af4a862ae36be7e82025-08-20T02:56:15ZengNature Portfolionpj Breast Cancer2374-46772025-03-011111810.1038/s41523-025-00741-yDynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsiesYael Bar0Geoffrey Fell1Aylin Dedeoglu2Natalie Moffett3Neelima Vidula4Laura Spring5Seth A. Wander6Aditya Bardia7Naomi Ko8Beverly Moy9Leif W. Ellisen10Steven J. Isakoff11Massachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterSection of Hematology/Oncology, Department of Medicine, Boston University School of MedicineMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Cancer CenterAbstract Trastuzumab deruxtecan (T-DXd) is approved for HER2-low (HER2 immunohistochemistry (IHC)1+ or 2+ with non-amplified in situ hybridization (ISH)), but not HER2-0 (IHC 0) metastatic breast cancer. The impact of repeat biopsies (Bxs) in identifying new potential candidates with triple negative breast cancer (TNBC) for T-DXd treatment remains unknown. 512 consecutive patients with TNBC at diagnosis were included in the study cohort. Bxs were categorized as core, surgical, or metastatic based on the timing and method of biopsy (Bx) acquisition, and the total number of Bxs was determined for each patient. Additionally, matched biopsies were identified, and the rate of discordance in HER2 status was calculated. The proportion of patients with at least one HER2-low result increased as the number of successive Bxs increased [59%, 73%, 83%, 83%, and 100% when 1 (196 patients), 2 (231 patients), 3 (48 patients), 4 (29 patients), and ≥ 5 (8 patients) Bxs were obtained, respectively]. Among patients without a prior HER2-low result, approximately one-third demonstrated HER2-low status with each additional successive Bx. HER2 status exhibited variability between matched Bxs, with observed discordance rates of 26%, 44%, and 33% between matched core-surgical, early-metastatic, and two metastatic matched Bxs, respectively. Our findings indicate that HER2 status can vary between different Bxs taken during the disease course of patients with TNBC with the highest discordance rate observed between the primary and metastatic Bxs. For patients with metastastic HER2-0 TNBC, repeat Bxs can increase the chance of obtaining a HER2-low result, thereby offering patients a promising therapeutic option.https://doi.org/10.1038/s41523-025-00741-y |
| spellingShingle | Yael Bar Geoffrey Fell Aylin Dedeoglu Natalie Moffett Neelima Vidula Laura Spring Seth A. Wander Aditya Bardia Naomi Ko Beverly Moy Leif W. Ellisen Steven J. Isakoff Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies npj Breast Cancer |
| title | Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies |
| title_full | Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies |
| title_fullStr | Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies |
| title_full_unstemmed | Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies |
| title_short | Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies |
| title_sort | dynamic her2 low status among patients with triple negative breast cancer tnbc and the impact of repeat biopsies |
| url | https://doi.org/10.1038/s41523-025-00741-y |
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